BACKGROUND AND INTRODUCTION Rates of perinatal HIV transmission have declined significantly due to progress in implementing interventions for the prevention of mother-to-child transmission. Despite this advance, there were still 150,000 new HIV infections in children worldwide in 2015. Furthermore, 1.8 million children under the age of 15 years were estimated to be living with HIV in 2015. In 2013, there were an estimated 11,130 individuals living with perinatal HIV infection in the United States. These youth and young adults would benefit greatly from treatments leading to HIV remission. Despite recent progress in understanding HIV-1 persistence in reservoirs, a definitive strategy to induce HIV-1 remission remains elusive. The central nervous system (CNS) represents a potential reservoir for HIV-1 that may need to be specifically targeted by remission strategies. The CNS also represents a site where strategies to activate latent HIV-1 and/or kill HIV-1-infected cells may be more likely to cause adverse outcomes. HIV-1 infects the CNS early during infection and predominantly targets perivascular macrophages, microglia, and astrocytes. The long half-life of these infected cells, reduced immunosurveillance in the CNS, and reduced penetration of some antiretroviral drugs into the CNS all may contribute to HIV-1 persistence in the CNS. As a result, the CNS is hypothesized to serve as a sanctuary site and reservoir for HIV-1 during antiretroviral treatment (ART), which could represent an important barrier to HIV-1 remission. Furthermore, strategies designed to induce remission may cause neuroinflammation and/or CNS toxicity, which will need to be monitored. There are several reasons to be specifically concerned about the CNS as an HIV-1 reservoir in perinatal infection. In perinatally-infected children, increased risk for impaired neurocognitive function is well documented, although this observation is confounded by the fact that perinatally-exposed uninfected children also have poor neurocognitive outcomes. The blood-brain barrier is less stringent in neonates and this may contribute to increased entry of HIV-1 into the CNS of perinatally-infected youth prior to ART initiation. Early in the epidemic, analyses of cerebrospinal fluid (CSF) were performed in adults and children as part of ART trials, but there are limited published data about HIV-1 in the CSF of perinatallyinfected individuals and no data for children on suppressive ART. The one pediatric study to compare HIV-1 in CSF and plasma was conducted in viremic individuals not on ART and found CSF compartmentalization based on virus sequencing. More recently, neuroimaging in perinatally-infected youth has identified differences in white matter microstructure and functional connectivity (distinct from uninfected youth) that correlate with HIV-1 disease severity, nadir CD4 percentage, and level of peak plasma viremia. Together, these findings support the direct effects of HIV-1 on the CNS in perinatal infection. However, no studies have focused on the HIV-1 reservoir in the CNS of ART-treated perinatally-infected youth and young adults. This study will begin to address that important gap by determining the prevalence of HIV-1 RNA and DNA in the CSF of perinatally-infected youth and young adults on suppressive ART as an initial assessment of CNS reservoirs in this population. This study will investigate the HIV-1 reservoir in the CNS of perinatally-infected youth and young adults on suppressive ART through examination of the CSF for persistence of HIV-1 RNA or DNA despite treatment with ART and for evidence of intrathecal inflammation. Perinatally infected youth and young adults are of particular interest because there are very limited CSF data available in this population and there are reasons to be concerned about the CNS reservoir in this population. In addition, measures of HIV-1 RNA in the CSF and associated biomarkers have not previously been explored in this population. A better understanding of viral persistence in the CSF, as well as CSF biomarker profiles, will provide preliminary data to move the field forward in understanding the role of the CNS in HIV-1 persistence and will have implications for future HIV-1 remission research in perinatal infection. Objectives Purpose: To assess the HIV-1 reservoir in the central nervous system (CNS) of perinatally HIV-1-infected youth and young adults. Findings from this study will advance understanding of the role of the CNS in HIV-1 persistence and its implications for future HIV-1 remission research. Design: Cross-sectional, multi-site, exploratory, observational study. Study Population: Perinatally HIV-1-infected youth and young adults (13-24 years of age) with cognitive impairment, on suppressive antiretroviral therapy, from study sites in the United States. Sample Size: Up to 45 to achieve 30 with plasma HIV-1 RNA of less than 20 copies/ml and the required volume of cerebrospinal fluid (CSF) collected for study purposes. Study Intervention: Not applicable, no intervention. Study Duration: Approximately 12 months. Accrual is expected to require up to nine months (from the date of first enrollment). Each participant will undergo all required study procedures within a 30-day period. After all participants have completed the required evaluations, specimen testing is expected to be completed within approximately three months. Primary Objective The primary objective of this study is to assess CSF HIV-1 reservoirs among the study population described above by determining the: ? Prevalence of quantifiable cell-free HIV-1 RNA in CSF ? Prevalence of detectable HIV-1 DNA in CSF cell pellets. Secondary Objective The secondary objective of this study is to assess for associations of CSF HIV-1 reservoirs among the study population described above with: ? Concentrations of inflammatory and neuronal injury biomarkers in CSF ? Concentrations of inflammatory and neuronal injury biomarkers in plasma Other objectives of this study are to assess for associations of CSF HIV-1 reservoirs among the study population described above with: ? Neuropsychological functioning of the study population, based on standardized testing ? Antiretroviral drug levels in hair